BRAF gene mutation in Iranian familial colorectal cancer patients at risk for Lynch syndrome.

Introduction: BRAF mutation is known as a surrogate marker for the promoter hypermethylation of MLH1 in sporadic colorectal cancer (s-CRC) with tumor microsatellite instability (MSI) versus wild type BRAF in the Lynch syndrome (LS) as a common hereditary cancer predisposing condition. Given the lack of enough information regarding the clinicopathological features of the disease and its molecular aspects among the Iranian populations, this study was launched in the Central Iran. Methods: In this descriptive study, 31 familial CRC probands recruited according to Amsterdam II criteria in Isfahan province (Central Iran). MSI testing and Immunohistochemistry (IHC) staining of four mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2 had been previously performed on their tumor DNAs and the adjacent healthy tissues. Finally, all DNA tumors were assessed for BRAF mutations by Sanger sequencing of the gene. Results: None of 31 probands presented BRAF mutations in their colorectal tumor. Of these cases, 7 patients (22.6%) showed MMR deficiency according to both MSI testing and IHC-MMR staining and 24 patients (77.4%) were MMR proficient. Colorectal tumor was more prevalent among MMR-deficient families (67.5% vs 27.9%). Gastric cancer was the most frequent extracolonic cancer in both groups ( 26.7% vs 16.5%). Conclusion: Wild-type BRAF in tumor DNA of the studied familial CRC probands at-risk for LS showed the necessity of more advanced molecular study to explore molecular background of the disease and the resistance to anti-EGFR drugs, as a new targeted therapy. [ABSTRACT FROM AUTHOR]